HIstamine receptors Blockers-COMP Flashcards
Histamine is a natural occurring
Does histamine cross the BBB?
Amine
- Does not cross the BBB
Histamine and inflammation
Found where?
Act as a mediator for inflammation in allergic disease
- Found in mast cells of skin. lungs and GIT
H1 receptors does what?
H2 receptors does what?
H1- Smooth muscle contraction in respiratory and GI tract
H2- Increase myocardial contractility and Heart
H3 receptors
cause inhibition, synthesis and release of histamine
Activitiy of H3 receptors may be
Impaired by H2 receptors.
Impairment of H3 receptors by H2 antagonists may result in an
Increase relase of histamine when a drug that cause histamine is given to a patient that was pre-treated with H2 antagonist alone
Histamine profound effect of
CV, airways and gastric H+ ions
Does histamine cross BBB
no
Predominant CV effect of histamine
Dilation of arterioles and capillaries leading to flushing decrease in PVR and Systemic BP and increase capillary permeability
Vascular effects are from direct effect of histamine on
Blood vessels mediated by H1 and H2
H2 receptor are activated at higher histamine concentrations
Slower onset and result in sustained vasodilation
H2 on conduction
Slow conduction of cardiac impulses through the AV node due to activation of H1 receptors
Zantac too quickly
Arrythmias
Positive chronotropic, inotropic effects and cardiac dysrhythmias are due to activation of
H2 receptors in the heart as well as the release of catecholamines from the adrenal medulla
Histamine in LARGE DOSES stimulates_____and_________ in the adrenal medulla, evoking the release of catecholamines.
ganglion cells and chromaffin cells
Pt with obstructive airway disease such as
Asthma and bronchitis are more likely to develop an increase in airway resistance in response to histamine
For AnTICHOLINERGIC and gastric secretions
high doses to affect GI secretions
Cholinergic blockade
Decrease the gastric secretory response to histamine
Bronchoconstriction is
Not prevented
Clinical use of the drug
Assess ability of gastric pariety cells to secrete H+
to determine parietal cell mass
Histamine with zollinger ellison
Hypersecretion of H+ ions in response to histamine in presence with zollinger ellison syndrome.
Histamine Receptor Antagonists
Class H1 or class H2
Histamine Receptor Antagonists act by
occupying receptors on effector cell membranes.
• For antihistamines this is a competitive and reversible interaction.
• H1 and H2 do not
inhibit the release of histamine.
H1 Receptor antagonist classified as
1st and 2nd generation
At low concentratons H1 antagonist act as
Competitive ANTAGONISTS
Most antihistamines are metabolized by:
hepatic microsomal enzymes.
Anticholinergic effects include;
dry mouth, blurred vision, urinary retention, and impotence may occur.
CNS effects of 1st generation
Sedation
CNS effects of 2nd generation
Non sedation
First generation H1 antagonist may also block
muscarinic cholinergic, 5-hydroxytryptomine (serotonin), or alpha-adrenergic receptors.
Levaquin
Can prolong QT
Short duration of Action
Benadryl
Most potent
Famodidine (Pepcid)
Least potent
(Cimetidine) Tagammet
Histamine and vascular endothelium to
stimulate release nitric oxide, which stimulates guanylate cyclase to increase levels of GMP in vascular smooth muscle, causing vasodilation
The release of prostacyclin from vascular endothelium is mediated by which receptor?
H1 receptors
Histamine activates the enzyme ________which leads to the release of ________
phospholipase; prostacyclin
The histamine-induced effects mediated by H1 receptors are
blocked by H1 receptor blockers.
Vascular effects of histamine are mediated by
H1 and H2 receptors
Which receptors are activated at lower concentrations?
H1 receptors: effects rapid and transient
Which receptors are activated at Higher concentrations?
H2 receptors
Slowed conduction of cardiac impulses through the AV node is due to
activation of H1 receptors.
Coronary artery vasoconstriction is mediated by and
H1 receptors,
Coronary artery vasodilation is mediated by
H2 receptors.
Decrease in systemic BP induced by histamine are prevented by
prior administration of the combination of H1 and H2 receptor antagonist.
Blocking either receptor alone
does not completely prevent the hypotensive effects of histamine
The presence of vagal activity results in even higher rate
hydrogen ion secretion.
Anacidity or hyposecretion of hydrogen ions in response to histamine may reflect
pernicious anemia, atrophic gastritis or gastric carcinoma.
At low concentrations H1 antagonist act as
competitive antagonist.
At high concentrations second generation H1 antagonist can act as
non-competitive antagonist.
H2 antagonists with mild sedative effects
Cimetidine
H1 Antagonists Marked anticholinergic effects
Benadryl (diphenhydramine)
Phenergan (Promethazine)
H1 antagonists with marked SEDATIVE effects
Benadryl (diphenhydramine)
H1 antagonists with marked ANTIEMETIC effects
Promethazine (Phenergan)
H1 antagonists with MODERATE ANTIEMETIC effects
Diphenhydramine (Benadryl)
Promethazine (Phenergan) Duration of action
4 to 24 hours
H2 antagonists medications are
Cimetidine, ranitidine, famotidine, and nizatidine
H2 antagonists are _______and _______inhibition of
that produce selective and reversible inhibition of H2 mediated secretion of acidic gastric fluid.
The histamine receptors on membranes of the acid-secreting parietal cells are of the ___type and are therefore not blocked by____ antagonists
H2; H1 antagonist
The occupation of H2 receptors by histamine released by mast cells and possibly other cells
activates adenylate cyclase, increasing the concentration of cAMP.
The occupation of H2 receptors, The increase in cAMP activates the
proton pump of the gastric parietal cells to secrete hydrogen ions against a large concentration gradient
The principal method of clearance from the plasma of oral doses of cimetidine, ranitidine, and famotidine
Hepatic metabolism
Renal clearance is the principal method for oral
doses of
nizatidine
The dose of cimetidine should be decreases in
patients with hepatic disease to avoid mental confusion.
Renal failure increases the elimination half life of
the H2 antagonist with the greatest effect on famotidine and nizatidine.
Decreases in dose are recommended for all of the
H2 antagonist for patients with renal failure.
Duodenal ulcers associated with
hypersecretion of gastric hydrogen ions.
In the preoperative period H2 antagonist are used to
increase the pH of gastric fluid before induction of anesthesia.
H2 antagonist are useful agents to decrease the risk of .
acid pneumonitis if inhalation of acidic gastric fluid occurs in the perioperative period
___________prior to induction, with or without a similar dose the evening prior to surgery.
Cimetidine 300mg orally 1.5-2 hours
H-2 antagonist ability to decrease the
volume of gastric fluid has been unpredictable
H2 antagonist have no influence on the
pH of the fluid already present in the stomach
Preoperative preparation of patients with allergic histories or patients undergoing procedures with an increase likelihood of allergic reactions (radiographic contrast dyes) may include prophylactic oral administration of an
H1 antagonist ( diphenhydramine 0.5-1mg/kg) AND an H2 antagonist (cimetidine 4mg/kg) every 6 hours in the 12 to 24 hour period prior to the event
H2 antagonist can be used in combination with an H1 antagonist to prevent the effects of histamine releasing drugs such as
morphine or atracurium, mivacurium, or protamine.
H2 antagonists Most common side effects include
diarrhea, headache, fatigue, and muscle pain
_______and _______ are associated with rapid IV administration of these agents most often to the elderly of critically ill.
Bradycardia and hypotension
Numerous drug interactions have been described between H-2 antagonist .
most commonly cimetidine. •
H2 antagonists The principal mechanism is impairment of
hepatic microsomal (cytochrome p-450) enzymes by cimetidine.
Cimetidine inhibits metabolism of drugs such as
propranolol, and diazepam that undergo high hepatic extraction.
Drugs that eliminated byare not effected
conjugation (oxazepam, lorazepam)
Cimetidine may increase the toxicity of
lidocaine
Cimetidine modestly decreases_________ and
deflurination of methoxyflurane; inhibits oxidative metabolism of halothane.
Ranitidine has less potential than cimetidine to alter
hepatic enzymes.
Famotidine and nizatidine do not
bind to hepatic enzymes
Cimetidine and ranitidine can impair renal tubular secretion of
procainamide and theophylline.
Magnesium and aluminum containing antacids can
decrease the absorption of the H2 antagonist.
Proton Pump Inhibitors
Drugs that provides prolonged inhibition of gastric acid secretion, regardless of the stimulus.
PPI These agents work by:
inhibiting gastric parietal cell hydrogen-potassium ATPase (PPI).
Daytime and nocturnal acid secretion and meal
stimulated acid secretion are inhibited to a greater degree with PPI then with H2 antagonist.
Currently the best treatment for Zollinger-Ellison syndrome.
PPI
Lansoprazole is available in a
suspension form
Pantoprazole is available in
IV formulation.
Omeprazole or esomeprazole capsules can be opened and the
granules can be placed into sodium bicarbonate.
Most common adverse reactions of PPI include; –
headache, and diarrhea
Serious but rare adverse reactions include
– Blood dyscrasia – Hepatic dysfunction – Stevens Johnson syndrome – Erythema multiforme – Pancreatitis
Studies with omeprazole suggest that this agent should be given
> 3 hours prior to induction of anesthesia in order to be effective.
Cromolyn inhibits antigen-induced release of histamine and other autacoids, including
leukotrienes from pulmonary mast cells, as well as from mast cells at other sites.
Cromolyn is used in the prophylactic treatment of asthma and has
no role in the treatment of an acute asthmatic attack.
Cromolyn does not
prevent the release of histamine from basophils, and cromolyn does not relax bronchial or vascular smooth muscle
